Animal models of tinnitus and the effects of noise exposure on non-classical auditory brain structures

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Abstract

Exposure to high-intensity noise has long been known to cause damage to the central and peripheral auditory systems, and often results in auditory pathologies such as tinnitus. Subjective tinnitus is often described as a ringing or buzzing sensation in one or both ears or emanating from inside the head in the absence of an external sound, and can be a severely debilitating condition for some individuals. In order to study the underlying mechanisms and potential therapeutic treatments for tinnitus, a number of animal behavioral models have been developed. When critically evaluating such paradigms, it is vital to consider a number of important factors including whether the behavioral paradigm mirrors what we know about tinnitus from the human condition, and whether it is resistant to confounding influences that accompany the tinnitus induction method. A major aim of this dissertation is to provide a critical evaluation of current animal behavioral models of tinnitus, with a special focus on the gap-startle paradigm which has become the most widely used method of screening animals for the presence of tinnitus. In addition to inducing tinnitus in animal models via the resulting damage to the peripheral and central auditory pathway, intense noise exposure can also result in damage in non-classical auditory regions of the brain. The hippocampus is one non-classical auditory structure that is particularly sensitive to noise exposure, with a single unilateral noise exposure capable of causing a long-term reduction of hippocampal neurogenesis. A second aim of this dissertation is to investigate the effects of intense noise exposure via blast waves on hippocampal neurogenesis and the underlying mechanisms of noise-induced suppression of neurogenesis.